MOLECULAR SCANNING FOR MUTATIONS IN THE BETA(3)-ADRENERGIC RECEPTOR GENE IN NAURUANS WITH OBESITY AND NONINSULIN-DEPENDENT DIABETES-MELLITUS

We recently identified a mutation in the human beta(3)-adrenergic rece ptor (beta(3)AR) gene (codon 64 TGG(Trp) --> CGG(Arg); TRP64ARG) that associates with features of the insulin resistance syndrome and an ear lier onset of noninsulin-dependent diabetes mellitus (NIDDM). We scann ed the beta(3)AR gene for mutations by single stranded conformational polymorphism analysis in 20 Nauruans with obesity and NIDDM. No mutati ons were identified. Sixty-five Nauruan subjects were genotyped for th e TRP64ARG beta(3)AR. All subjects were homozygous for the normal alle le. We genotyped Samoans and Asians for the TRP64ARG beta(3)AR. Seven of 52 Samoans were heterozygous for the mutant arginine allele (allele frequency, 0.07). Of these, 5 were diabetic and 2 were nondiabetic (b y Fisher's exact test, P = 0.4). There were trends toward increased bo dy mass indices, waist to hip ratios, and 2-h insulin levels during or al glucose tolerance tests in Samoans with the mutation; however, the limited number of subjects available for study precluded rigorous stat istical analysis. The TRP64ARG beta(3)AR was also detected in Chinese, Chinese Americans, and subjects from the Indian subcontinent. In conc lusion, the TRP64ARG beta(3)AR mutation or any other mutation in the b eta(3)AR gene is not a major contributor to genetic susceptibility to NIDDM and obesity likely in Nauruans.